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Neuron Feb 2024In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in...
In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in disparate locations is not understood. Using task-based fMRI and multimodal PET imaging, we assess the impact of local AD pathology on network-to-network interactions. We show that AD pathologies flip interactions between the default mode network (DMN) and the medial temporal lobe (MTL) from inhibitory to excitatory. The DMN is hyperexcited with increasing levels of Aβ, which drives hyperexcitability within the MTL and this directed hyperexcitation of the MTL by the DMN predicts the rate of tau accumulation within the EC. Our results support a model whereby Aβ induces disruptions to local excitatory-inhibitory balance in the DMN, driving hyperexcitability in the MTL, leading to tau accumulation. We propose that Aβ-induced disruptions to excitatory-inhibitory balance is a candidate causal route between Aβ and remote EC-tau accumulation.
Topics: Humans; tau Proteins; Default Mode Network; Alzheimer Disease; Amyloid beta-Peptides; Entorhinal Cortex; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 38096815
DOI: 10.1016/j.neuron.2023.11.014 -
Frontiers in Endocrinology 2023Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the...
BACKGROUND
Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the impact of NAFLD on cerebral cortical structure and specific affected brain regions remains unclear. Therefore, we aimed to explore the potential causal relationship between NAFLD and cerebral cortical structure.
METHODS
We conducted a Mendelian randomization (MR) study using genetic predictors of alanine aminotransferase (ALT), NAFLD, and percent liver fat (PLF) and combined them with genome-wide association study (GWAS) summary statistics from the ENIGMA Consortium. Several methods were used to assess the effect of NAFLD on full cortex and specific brain regions, along with sensitivity analyses.
RESULTS
At the global level, PLF nominally decreased SA of full cortex; at the functional level, ALT presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars orbitalis, and TH of pericalcarine cortex. Besides, NAFLD presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars triangularis and TH of pericalcarine cortex, but increased TH of entorhinal cortex, lateral orbitofrontal cortex and temporal pole. Furthermore, PLF presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of cuneus and lingual gyrus, but increased TH of entorhinal cortex.
CONCLUSION
NAFLD is suggestively associated with atrophy in specific functional regions of the human brain.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Mendelian Randomization Analysis; Genome-Wide Association Study; Magnetic Resonance Imaging; Cerebral Cortex
PubMed: 38027213
DOI: 10.3389/fendo.2023.1276576 -
ELife Jan 2023Blocking the activity of neurons in a region of the brain involved in memory leads to cell death, which could help explain the spatiotemporal disorientation observed in...
Blocking the activity of neurons in a region of the brain involved in memory leads to cell death, which could help explain the spatiotemporal disorientation observed in Alzheimer's disease.
Topics: Humans; Entorhinal Cortex; Alzheimer Disease; Neurons; Brain; Head
PubMed: 36692286
DOI: 10.7554/eLife.85437 -
Annual Review of Vision Science Sep 2019Humans are remarkably adept at perceiving and understanding complex real-world scenes. Uncovering the neural basis of this ability is an important goal of vision... (Review)
Review
Humans are remarkably adept at perceiving and understanding complex real-world scenes. Uncovering the neural basis of this ability is an important goal of vision science. Neuroimaging studies have identified three cortical regions that respond selectively to scenes: parahippocampal place area, retrosplenial complex/medial place area, and occipital place area. Here, we review what is known about the visual and functional properties of these brain areas. Scene-selective regions exhibit retinotopic properties and sensitivity to low-level visual features that are characteristic of scenes. They also mediate higher-level representations of layout, objects, and surface properties that allow individual scenes to be recognized and their spatial structure ascertained. Challenges for the future include developing computational models of information processing in scene regions, investigating how these regions support scene perception under ecologically realistic conditions, and understanding how they operate in the context of larger brain networks.
Topics: Animals; Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Occipital Lobe; Parahippocampal Gyrus; Spatial Navigation; Visual Cortex; Visual Perception
PubMed: 31226012
DOI: 10.1146/annurev-vision-091718-014809 -
Nature Communications Oct 2023Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic...
Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval.
Topics: Hippocampus; Neurons; Entorhinal Cortex; Theta Rhythm; Parvalbumins; Action Potentials; CA1 Region, Hippocampal
PubMed: 37816713
DOI: 10.1038/s41467-023-41746-0 -
Current Opinion in Neurobiology Oct 2020The hippocampus performs two complementary processes, pattern separation and pattern completion, to minimize interference and maximize the storage capacity of memories.... (Review)
Review
The hippocampus performs two complementary processes, pattern separation and pattern completion, to minimize interference and maximize the storage capacity of memories. Classic computational models have suggested that the dentate gyrus (DG) supports pattern separation and the putative attractor circuitry in CA3 supports pattern completion. However, recent evidence of functional heterogeneity along the CA3 transverse axis of the hippocampus suggests that the DG and proximal CA3 work as a functional unit for pattern separation, while distal CA3 forms an autoassociative network for pattern completion. We propose that the outputs of these functional circuits, combined with direct projections from entorhinal cortex to CA1, form interconnected, parallel processing circuits to support accurate memory storage and retrieval.
Topics: Dentate Gyrus; Entorhinal Cortex; Hippocampus; Memory
PubMed: 32502734
DOI: 10.1016/j.conb.2020.03.004 -
Nature Dec 2021Could learning that uses cognitive control to judiciously use relevant information while ignoring distractions generally improve brain function, beyond forming explicit...
Could learning that uses cognitive control to judiciously use relevant information while ignoring distractions generally improve brain function, beyond forming explicit memories? According to a neuroplasticity hypothesis for how some cognitive behavioural therapies are effective, cognitive control training (CCT) changes neural circuit information processing. Here we investigated whether CCT persistently alters hippocampal neural circuit function. We show that mice learned and remembered a conditioned place avoidance during CCT that required ignoring irrelevant locations of shock. CCT facilitated learning new tasks in novel environments for several weeks, relative to unconditioned controls and control mice that avoided the same place during reduced distraction. CCT rapidly changes entorhinal cortex-to-dentate gyrus synaptic circuit function, resulting in an excitatory-inhibitory subcircuit change that persists for months. CCT increases inhibition that attenuates the dentate response to medial entorhinal cortical input, and through disinhibition, potentiates the response to strong inputs, pointing to overall signal-to-noise enhancement. These neurobiological findings support the neuroplasticity hypothesis that, as well as storing item-event associations, CCT persistently optimizes neural circuit information processing.
Topics: Animals; Avoidance Learning; CA1 Region, Hippocampal; Cognition; Cognitive Behavioral Therapy; Conditioning, Operant; Dentate Gyrus; Entorhinal Cortex; Female; GABAergic Neurons; Hippocampus; Long-Term Potentiation; Male; Memory; Mice; Mice, Inbred C57BL; Models, Neurological; Neural Inhibition; Neural Pathways; Neuronal Plasticity; Spatial Processing; Synapses
PubMed: 34759316
DOI: 10.1038/s41586-021-04070-5 -
Developmental Neurobiology 2023Social memories formed in early life, like those for family and unrelated peers, are known to contribute to healthy social interactions throughout life, although how the... (Review)
Review
Social memories formed in early life, like those for family and unrelated peers, are known to contribute to healthy social interactions throughout life, although how the developing brain supports social memory remains relatively unexplored. The CA2 subregion of the hippocampus is involved in social memory function, but most literature on this subject is restricted to studies of adult rodents. Here, we review the current literature on the embryonic and postnatal development of hippocampal subregion CA2 in mammals, with a focus on the emergence of its unusual molecular and cellular characteristics, including its notably high expression of plasticity-suppressing molecules. We also consider the connectivity of the CA2 with other brain areas, including intrahippocampal regions, such as the dentate gyrus, CA3, and CA1 regions, and extrahippocampal regions, such as the hypothalamus, ventral tegmental area, basal forebrain, raphe nuclei, and the entorhinal cortex. We review developmental milestones of CA2 molecular, cellular, and circuit-level features that may contribute to emerging social recognition abilities for kin and unrelated conspecifics in early life. Lastly, we consider genetic mouse models related to neurodevelopmental disorders in humans in order to survey evidence about whether atypical formation of the CA2 may contribute to social memory dysfunction.
Topics: Humans; Mice; Animals; CA2 Region, Hippocampal; Hippocampus; Recognition, Psychology; Entorhinal Cortex; CA1 Region, Hippocampal; Mammals
PubMed: 37326250
DOI: 10.1002/dneu.22919 -
Neuroscience Bulletin Aug 2020
Topics: Alzheimer Disease; Biomarkers; Humans; Memory Disorders; Neuropsychological Tests; Parahippocampal Gyrus; Prefrontal Cortex
PubMed: 32743769
DOI: 10.1007/s12264-020-00560-0 -
Scientific Data Sep 2023Alzheimer's disease (AD) is the most common form of dementia worldwide, with a projection of 151 million cases by 2050. Previous genetic studies have identified three...
Alzheimer's disease (AD) is the most common form of dementia worldwide, with a projection of 151 million cases by 2050. Previous genetic studies have identified three main genes associated with early-onset familial Alzheimer's disease, however this subtype accounts for less than 5% of total cases. Next-generation sequencing has been well established and holds great promise to assist in the development of novel therapeutics as well as biomarkers to prevent or slow the progression of this devastating disease. Here we present a public resource of functional genomic data from the parahippocampal gyrus of 201 postmortem control, mild cognitively impaired (MCI) and AD individuals from the Mount Sinai brain bank, of which whole-genome sequencing (WGS), and bulk RNA sequencing (RNA-seq) were previously published. The genomic data include bulk proteomics and DNA methylation, as well as cell-type-specific RNA-seq and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data. We have performed extensive preprocessing and quality control, allowing the research community to access and utilize this public resource available on the Synapse platform at https://doi.org/10.7303/syn51180043.2 .
Topics: Humans; Alzheimer Disease; Biological Assay; Multiomics; Parahippocampal Gyrus
PubMed: 37684260
DOI: 10.1038/s41597-023-02507-2